Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29792 | 89599;89600;89601 | chr2:178553631;178553630;178553629 | chr2:179418358;179418357;179418356 |
| N2AB | 28151 | 84676;84677;84678 | chr2:178553631;178553630;178553629 | chr2:179418358;179418357;179418356 |
| N2A | 27224 | 81895;81896;81897 | chr2:178553631;178553630;178553629 | chr2:179418358;179418357;179418356 |
| N2B | 20727 | 62404;62405;62406 | chr2:178553631;178553630;178553629 | chr2:179418358;179418357;179418356 |
| Novex-1 | 20852 | 62779;62780;62781 | chr2:178553631;178553630;178553629 | chr2:179418358;179418357;179418356 |
| Novex-2 | 20919 | 62980;62981;62982 | chr2:178553631;178553630;178553629 | chr2:179418358;179418357;179418356 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs876658091  |
0.096 | 0.999 | N | 0.723 | 0.381 | 0.421799068777 | gnomAD-2.1.1 | 1.07E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.56E-05 | 1.40489E-04 |
| T/I | rs876658091 |
0.096 | 0.999 | N | 0.723 | 0.381 | 0.421799068777 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| T/I | rs876658091 |
0.096 | 0.999 | N | 0.723 | 0.381 | 0.421799068777 | gnomAD-4.0.0 | 3.34628E-05 | None | None | None | None | N | None | 1.33472E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 3.98364E-05 | 0 | 9.60615E-05 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1116 | likely_benign | 0.1007 | benign | -0.817 | Destabilizing | 0.767 | D | 0.264 | neutral | N | 0.434230983 | None | None | N |
| T/C | 0.4991 | ambiguous | 0.4806 | ambiguous | -0.575 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| T/D | 0.4701 | ambiguous | 0.4136 | ambiguous | -0.01 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| T/E | 0.3982 | ambiguous | 0.3594 | ambiguous | 0.049 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/F | 0.4217 | ambiguous | 0.3832 | ambiguous | -0.968 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| T/G | 0.2255 | likely_benign | 0.2212 | benign | -1.073 | Destabilizing | 0.997 | D | 0.611 | neutral | None | None | None | None | N |
| T/H | 0.3725 | ambiguous | 0.329 | benign | -0.985 | Destabilizing | 1.0 | D | 0.721 | prob.delet. | None | None | None | None | N |
| T/I | 0.3599 | ambiguous | 0.3093 | benign | -0.211 | Destabilizing | 0.999 | D | 0.723 | prob.delet. | N | 0.485430595 | None | None | N |
| T/K | 0.2809 | likely_benign | 0.2525 | benign | -0.342 | Destabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| T/L | 0.1762 | likely_benign | 0.1504 | benign | -0.211 | Destabilizing | 0.997 | D | 0.574 | neutral | None | None | None | None | N |
| T/M | 0.1263 | likely_benign | 0.1101 | benign | -0.358 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| T/N | 0.1432 | likely_benign | 0.1278 | benign | -0.536 | Destabilizing | 1.0 | D | 0.653 | neutral | N | 0.47007714 | None | None | N |
| T/P | 0.3313 | likely_benign | 0.2596 | benign | -0.383 | Destabilizing | 0.999 | D | 0.731 | prob.delet. | N | 0.5177723 | None | None | N |
| T/Q | 0.2984 | likely_benign | 0.2753 | benign | -0.527 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | N |
| T/R | 0.2738 | likely_benign | 0.2415 | benign | -0.15 | Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| T/S | 0.1434 | likely_benign | 0.1365 | benign | -0.864 | Destabilizing | 0.992 | D | 0.404 | neutral | N | 0.444890694 | None | None | N |
| T/V | 0.2454 | likely_benign | 0.2213 | benign | -0.383 | Destabilizing | 0.997 | D | 0.459 | neutral | None | None | None | None | N |
| T/W | 0.7683 | likely_pathogenic | 0.7363 | pathogenic | -0.998 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| T/Y | 0.429 | ambiguous | 0.4026 | ambiguous | -0.681 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.